Abstract | BACKGROUND & AIMS: METHODS: The role of STAT3 in alcoholic liver injury was investigated in hepatocyte-specific STAT3 knockout (H-STAT3KO) mice and macrophage/neutrophil-specific STAT3 KO (M/N-STAT3KO) mice. Alcoholic liver injury was achieved by feeding mice a liquid diet containing 5% ethanol for up to 8 weeks. RESULTS: Compared with wild-type mice, feeding H-STAT3KO mice with an ethanol-containing diet induced greater hepatic steatosis, hypertriglyceridemia, and hepatic expression of lipogenic genes ( sterol regulatory element-binding protein, fatty acid synthase, acetyl-CoA carboxylase-1, and stearoyl-CoA desaturase 1), but less inflammation and lower expression of hepatic proinflammatory cytokines. In contrast, ethanol-fed M/N-STAT3KO mice showed more hepatic inflammation, worse injury, and increased hepatic expression of proinflammatory cytokines compared with wild-type mice. Kupffer cells isolated from ethanol-fed H-STAT3KO mice produced similar amounts of reactive oxygen species and tumor necrosis factor alpha, whereas Kupffer cells from M/N-STAT3KO mice produced more reactive oxygen species and tumor necrosis factor alpha compared with wild-type controls. CONCLUSIONS:
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Authors | Norio Horiguchi, Lei Wang, Partha Mukhopadhyay, Ogyi Park, Won Il Jeong, Fouad Lafdil, Douglas Osei-Hyiaman, Akira Moh, Xin Yuan Fu, Pál Pacher, George Kunos, Bin Gao |
Journal | Gastroenterology
(Gastroenterology)
Vol. 134
Issue 4
Pg. 1148-58
(Apr 2008)
ISSN: 1528-0012 [Electronic] United States |
PMID | 18395093
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Differentiation
- Ccr2 protein, mouse
- Central Nervous System Depressants
- RNA, Messenger
- Receptors, CCR2
- STAT3 Transcription Factor
- Stat3 protein, mouse
- Sterol Regulatory Element Binding Protein 1
- monocyte-macrophage differentiation antigen
- Ethanol
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Topics |
- Animals
- Antigens, Differentiation
(biosynthesis, genetics)
- Blotting, Western
- Cell Proliferation
- Central Nervous System Depressants
(toxicity)
- Chronic Disease
- Disease Models, Animal
- Ethanol
(toxicity)
- Gene Expression Regulation
- Hepatocytes
(drug effects, metabolism, pathology)
- Immunohistochemistry
- Liver Cirrhosis, Alcoholic
(genetics, metabolism, pathology)
- Liver Cirrhosis, Experimental
(genetics, metabolism, pathology)
- Mice
- Mice, Knockout
- RNA, Messenger
(genetics)
- Receptors, CCR2
(biosynthesis, genetics)
- Reverse Transcriptase Polymerase Chain Reaction
- STAT3 Transcription Factor
(genetics, metabolism)
- Sterol Regulatory Element Binding Protein 1
(biosynthesis, genetics)
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